Evidence suggests that prenatal exposure to cocaine produces a permanent uncoupling of the dopamine D1 receptor from its G-protein in frontal and cingulate cortices and in caudate nucleus. Activation of D1 receptors during brain development exerts modulatory effects on neuronal development, and prenatal cocaine exposure has been shown to alter neuronal cytoarchitecture in brain regions receiving dopaminergic inputs, including frontal, entorhinal, and piriform cortices. D1 receptors are abundant in frontal cortex and appear to modulate neurocircuits that support the performance of tasks that tap executive functions. Prenatal cocaine exposure has been linked with deficits in executive cognitive capacities, such as allocation of attention, memory, and the ability to suppress processing of and responses to competing stimuli that, in humans, undergo important developmental changes during adolescence. Functional magnetic resonance imaging (fMRI) has demonstrated that performance of executive function tasks is associated with increased activation of fronto-striatal and fronto-parietal networks with increasing age during the adolescent developmental epoch. Event related potential (ERP) studies, have demonstrated consistent maturational changes in ERP morphology, amplitude and latency during performance of attention and executive function tasks. Diffusion tensor imaging (DTI), which provides quantitative measures of white matter microstructure, has demonstrated age related increases in fractional anisotropy, reflecting increases in myelination, in cortical and subcortical white matter pathways that correlate with age related changes in cognitive abilities. This proposal aims to develop and refine fMRI, DTI, and ERP methods for assessing the functional and structural integrity of neurocircuitry supporting selective and divided attention and verbal and visuospatial memory in adolescents with and without prenatal exposure to maternal cocaine use. This work will be performed in collaboration with Linda Mayes, MD, and will form the foundation for future planned projects that will examine the relationship between the integrity of these circuits and cognitive, academic, and psychosocial outcome in a sample of adolescents with and without prenatal exposure to maternal cocaine use that have been followed longitudinally from birth at the Yale Child Study Center (R01 DA-06025, PI: L.C. Mayes). PUBLIC HEALTH RELEVANCE: Children and adolescents with prenatal cocaine exposure have deficits in executive cognitive abilities, including allocation of attention, memory, and the ability to suppress processing of and responses to competing stimuli. This proposal will develop and refine fMRI, DTI, and ERP methods for assessing the function and structure of neurocircuitry supporting selective and divided attention and verbal and visuospatial memory in adolescents with and without prenatal exposure to maternal cocaine use. This work will form the foundation for future planned projects that will examine the relationship between the integrity of these circuits and cognitive, academic, and psychosocial outcome in a sample of adolescents with and without prenatal exposure to maternal cocaine use that have been followed longitudinally from birth at the Yale Child Study Center (R01 DA-06025, PI: L.C. Mayes). [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]